Acetaminophen And Codeine and Butalbital: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Butalbital
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Both of these medicines can slow down your brain and body. Your codeine (a narcotic pain reliever) and butalbital (a barbiturate often used for tension headaches) each cause drowsiness and can slow your breathing. When you take them together, those calming effects can add up, so you may feel very sleepy, dizzy, or foggy, and in serious cases your breathing could become dangerously slow.
The good news is your care team can manage this. Please don't stop either medicine on your own. Instead, talk with your doctor or pharmacist so they can use the lowest doses needed and keep a close eye on how you're doing.
Effect: Additive CNS and respiratory depression from combining butalbital (barbiturate) with an opioid-containing product (codeine plus acetaminophen).
- Mechanism: Pharmacodynamic additive CNS depression; no PK interaction implied.
- Direction: Enhanced sedation, hypoventilation, and respiratory depression risk.
- Onset: Unspecified; expect with concurrent dosing.
- Evidence: Theoretical, but severity rated major given additive respiratory risk.
- Management: Reserve concurrent use for patients lacking adequate alternatives. Limit dose and duration to the minimum required. Monitor for sedation and respiratory depression.
What happens
An increased risk of CNS depression
Interaction Deep Dive
Avoid concomitant use of butalbital with CNS depressants as this may enhance the effects of CNS depressants causing an increased risk of CNS depression1. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required and closely monitor for signs and symptoms of respiratory depression (including sedation) 2.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination can cause added drowsiness and slowed breathing, so your care team handles it carefully.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may use the lowest doses for the shortest time needed, and this can be individualized to you.
- They may monitor you more closely for heavy sedation or breathing trouble, especially when starting or increasing either medicine.
Get emergency help for very slow or shallow breathing, extreme sleepiness, confusion, or trouble waking up. Avoid alcohol and other sedating medicines, and ask your pharmacist before adding anything new.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Butalbital together?
Taking butalbital with codeine/acetaminophen adds up their sedating effects and can slow your breathing, so use the lowest effective doses and watch closely for heavy drowsiness. Keep both as prescribed and let your doctor or pharmacist coordinate the safest plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Butalbital interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Acetaminophen And Codeine and Butalbital interaction managed?
This combination can cause added drowsiness and slowed breathing, so your care team handles it carefully. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may use the lowest doses for the shortest time needed, and this can be individualized to you. They may monitor you more closely for heavy sedation or breathing trouble, especially when starting or in… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Butalbital need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Product Information: Butalbital acetaminophen oral tablets, butalbital acetaminophen oral tablets. Burel Pharmaceuticals LLC (per DailyMed), Mason, OH, 2022. DailyMed
- Product Information: Butalbital, Acetaminophen, Caffeine, Codeine Phosphate oral capsules, butalbital, acetaminophen, caffeine, codeine phosphate oral capsules. Actavis Pharma Inc (per FDA), Parsippany, NJ, 2023. DailyMed
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